Substrate Specificity and Structure of Human Aminoadipate Aminotransferase/kynurenine Aminotransferase II

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Bioscience Reports

DOI:https://doi.org/10.1042/BSR20080085· OSTI ID:960185

Han, Q; Cai, T; Tagle, D; Robinson, H; Li, J

KAT (kynurenine aminotransferase) II is a primary enzyme in the brain for catalysing the transamination of kynurenine to KYNA (kynurenic acid). KYNA is the only known endogenous antagonist of the N-methyl-D-aspartate receptor. The enzyme also catalyses the transamination of aminoadipate to a-oxoadipate; therefore it was initially named AADAT (aminoadipate aminotransferase). As an endotoxin, aminoadipate influences various elements of glutamatergic neurotransmission and kills primary astrocytes in the brain. A number of studies dealing with the biochemical and functional characteristics of this enzyme exist in the literature, but a systematic assessment of KAT II addressing its substrate profile and kinetic properties has not been performed. The present study examines the biochemical and structural characterization of a human KAT II/AADAT. Substrate screening of human KAT II revealed that the enzyme has a very broad substrate specificity, is capable of catalysing the transamination of 16 out of 24 tested amino acids and could utilize all 16 tested a-oxo acids as amino-group acceptors. Kinetic analysis of human KAT II demonstrated its catalytic efficiency for individual amino-group donors and acceptors, providing information as to its preferred substrate affinity. Structural analysis of the human KAT II complex with a-oxoglutaric acid revealed a conformational change of an N-terminal fraction, residues 15-33, that is able to adapt to different substrate sizes, which provides a structural basis for its broad substrate specificity.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 960185
• Report Number(s): BNL--83171-2009-JA
• Journal Information: Bioscience Reports, Journal Name: Bioscience Reports Journal Issue: 4 Vol. 28; ISSN 0144-8463; ISSN BRPTDT
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
AFFINITY
AMINO ACIDS
AMINOTRANSFERASES
BRAIN
CONFORMATIONAL CHANGES
EFFICIENCY
ENZYMES
FUNCTIONALS
KINETICS
KYNURENINE
RESIDUES
SPECIFICITY
SUBSTRATES
national synchrotron light source